PROMETH FORTIS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PROMETH FORTIS (PROMETH FORTIS).

How it works

Promethazine is a phenothiazine derivative that acts as a histamine H1 receptor antagonist, with additional anticholinergic, antiemetic, and sedative properties. It blocks histamine at H1 receptors, reducing allergic symptoms and motion sickness, and exerts antiemetic effects by blocking dopamine D2 receptors in the chemoreceptor trigger zone.

What the body does with it

Metabolism	Primarily metabolized in the liver via oxidation and conjugation, with involvement of CYP2D6 isoenzyme.
Excretion	Primarily renal as inactive metabolites; <1% excreted unchanged. Total elimination: renal ~70%, fecal ~30%.
Half-life	Terminal elimination half-life: 9–16 hours (mean ~12 hours). In children and elderly, half-life may be prolonged (up to 20 hours).
Protein binding	Protein binding: 93–98%, primarily to albumin.
Volume of Distribution	Volume of distribution: 10–15 L/kg (range 6–20 L/kg). Large Vd indicates extensive tissue distribution and penetration into CNS.
Bioavailability	Oral: ~25% (due to extensive first-pass metabolism); Intramuscular: ~75–80%; Rectal: ~25–30%.
Onset of Action	Oral: 15–60 minutes; Intramuscular: 20–30 minutes; Intravenous: 3–5 minutes; Rectal: 30–60 minutes.
Duration of Action	Oral: 4–6 hours; Intramuscular: 6–12 hours; Intravenous: 4–8 hours; Rectal: 4–6 hours. Clinical note: Duration varies with dose and indication; antiemetic effect may persist longer than sedative effect.

Classification & Brands

Dosing & administration

Adults: 12.5-25 mg intramuscular or intravenous every 4-6 hours as needed for nausea. For severe nausea up to 50 mg IM/IV. Maximum single dose 50 mg, maximum daily dose 200 mg.

Dosage form	SYRUP
Renal impairment	No specific guidelines; use caution in severe renal impairment (eGFR <30 mL/min) due to potential for accumulation and increased sedative effects; consider dose reduction or interval prolongation.
Liver impairment	Child-Pugh A: No adjustment necessary. Child-Pugh B: Consider 50% dose reduction and monitor. Child-Pugh C: Contraindicated or use with caution; avoid use if possible.
Pediatric use	Children >2 years: 0.25-0.5 mg/kg intramuscular or intravenous every 4-6 hours as needed, maximum 25 mg per dose. Alternatively: age 2-5 years: 5 mg IM/IV every 4-6 hours; 6-12 years: 10 mg IM/IV every 4-6 hours; >12 years: 12.5-25 mg IM/IV every 4-6 hours.
Geriatric use	Use lowest effective dose (e.g., 12.5 mg IM/IV every 6-8 hours) due to increased sensitivity to anticholinergic effects, sedation, and risk of falls; avoid in patients with dementia or cognitive impairment.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PROMETH FORTIS (PROMETH FORTIS).

Breastfeeding	Excreted in breast milk in low amounts; M/P ratio not established. American Academy of Pediatrics considers compatible with breastfeeding, but monitor infant for sedation or irritability.
Teratogenic Risk	First trimester: Limited human data; animal studies show no consistent teratogenicity. Second and third trimesters: May cause transient neonatal withdrawal symptoms (irritability, tremors) with prolonged use near term. No documented structural anomalies.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Promethazine should not be used in children younger than 2 years of age due to the risk of potentially fatal respiratory depression. Use in children aged 2 to 18 is also cautioned, with lowest effective dose recommended.

Side Effect Profile

Serious Effects

Absolute Contraindications

Comatose states, CNS depression from barbiturates or alcohol, severe hypotension, hypersensitivity to promethazine or other phenothiazines, use in children younger than 2 years, and intra-arterial or subcutaneous injection.

Clinical Precautions

Precautions

May cause severe respiratory depression, especially in children and in combination with other CNS depressants. Avoid use in patients with respiratory compromise. Use cautiously in patients with asthma, COPD, sleep apnea, or other respiratory conditions. May cause extrapyramidal reactions, neuroleptic malignant syndrome, and anticholinergic effects. May lower seizure threshold. Use caution in elderly patients. Avoid subcutaneous or intra-arterial administration due to tissue necrosis risk.

Clinical Tips & Counseling

Drug interactions

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PROMETH FORTIS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PROMETH FORTIS (PROMETH FORTIS).

How it works

What the body does with it

Metabolism	Primarily metabolized in the liver via oxidation and conjugation, with involvement of CYP2D6 isoenzyme.
Excretion	Primarily renal as inactive metabolites; <1% excreted unchanged. Total elimination: renal ~70%, fecal ~30%.
Half-life	Terminal elimination half-life: 9–16 hours (mean ~12 hours). In children and elderly, half-life may be prolonged (up to 20 hours).
Protein binding	Protein binding: 93–98%, primarily to albumin.
Volume of Distribution	Volume of distribution: 10–15 L/kg (range 6–20 L/kg). Large Vd indicates extensive tissue distribution and penetration into CNS.
Bioavailability	Oral: ~25% (due to extensive first-pass metabolism); Intramuscular: ~75–80%; Rectal: ~25–30%.
Onset of Action	Oral: 15–60 minutes; Intramuscular: 20–30 minutes; Intravenous: 3–5 minutes; Rectal: 30–60 minutes.
Duration of Action	Oral: 4–6 hours; Intramuscular: 6–12 hours; Intravenous: 4–8 hours; Rectal: 4–6 hours. Clinical note: Duration varies with dose and indication; antiemetic effect may persist longer than sedative effect.

Classification & Brands

Dosing & administration

Adults: 12.5-25 mg intramuscular or intravenous every 4-6 hours as needed for nausea. For severe nausea up to 50 mg IM/IV. Maximum single dose 50 mg, maximum daily dose 200 mg.

Dosage form	SYRUP
Renal impairment	No specific guidelines; use caution in severe renal impairment (eGFR <30 mL/min) due to potential for accumulation and increased sedative effects; consider dose reduction or interval prolongation.
Liver impairment	Child-Pugh A: No adjustment necessary. Child-Pugh B: Consider 50% dose reduction and monitor. Child-Pugh C: Contraindicated or use with caution; avoid use if possible.
Pediatric use	Children >2 years: 0.25-0.5 mg/kg intramuscular or intravenous every 4-6 hours as needed, maximum 25 mg per dose. Alternatively: age 2-5 years: 5 mg IM/IV every 4-6 hours; 6-12 years: 10 mg IM/IV every 4-6 hours; >12 years: 12.5-25 mg IM/IV every 4-6 hours.
Geriatric use	Use lowest effective dose (e.g., 12.5 mg IM/IV every 6-8 hours) due to increased sensitivity to anticholinergic effects, sedation, and risk of falls; avoid in patients with dementia or cognitive impairment.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PROMETH FORTIS (PROMETH FORTIS).

Breastfeeding	Excreted in breast milk in low amounts; M/P ratio not established. American Academy of Pediatrics considers compatible with breastfeeding, but monitor infant for sedation or irritability.
Teratogenic Risk	First trimester: Limited human data; animal studies show no consistent teratogenicity. Second and third trimesters: May cause transient neonatal withdrawal symptoms (irritability, tremors) with prolonged use near term. No documented structural anomalies.
Fetal Monitoring